SAKK 06/19 - Intravesical BCG followed by an immuno-chemotherapy in patients with operable muscle-invasive bladder cancer. A multicenter single-arm phase II study.

Identifiant de l'essai ICTRP
NCT04630730 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
SAKK 06/19 Intravesical recombinant BCG followed by perioperative chemo-immunotherapy for patients with muscle-invasive bladder cancer (MIBC). A multicenter, single-arm phase II trial (BASEC)

Titre académique
Intravesical Recombinant BCG (Bacillus Calmette Gurin) Followed by Perioperative Chemo-immunotherapy for Patients With Muscle-invasive Bladder Cancer (MIBC). A Multicenter, Single-arm Phase II Trial (ICTRP)

Titre public
Intravesical Recombinant BCG Followed by Perioperative Chemo-immunotherapy for Patients With MIBC (ICTRP)

Maladie en cours d'investigation
Bladder Cancer (ICTRP)

Intervention étudiée
Drug: Recombinant intravesical BCG (Bacillus Calmette-Gurin VPM1002BC)Drug: AtezolizumabDrug: CisplatinDrug: Gemcitabine (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Critères d'inclusion/exclusion
Inclusion Criteria:

- Written informed consent according to ICH/GCP regulations before registration and
prior to any trial specific procedures

- Histologically proven urothelial cell carcinoma of the bladder (cT2, cT3 or cT4a and
= cN1 (defined as a solitary lymph node = 2 cm in the greatest dimension) and cM0)
and be considered suitable for curative multimodality treatment including radical
cystectomy by a multidisciplinary tumor board

- All histological subtypes eligible with the exception of small cell component

- Age = 18 years

- WHO performance status 0-1

- Hematological function: hemoglobin = 90 g/L, neutrophils = 1.5 x 109/L, platelets =
100 x 109/L

- Hepatic function: total bilirubin = 1.5 x ULN (except for patients with Gilbert's
disease = 3.0 x ULN), AST = 2.5 x ULN and ALT = 2.5 x ULN, AP = 2.5 x ULN

- Renal function: estimated glomerular filtration rate (eGFR) > 50 mL/min/1.73m,
according to CKD-EPI formula

- Women of childbearing potential must use effective contraception, are not pregnant
or lactating and agree not to become pregnant during trial treatment and until 5
months after the last dose of investigational drug

- Men agree not to donate sperm or to father a child during trial treatment and until
5 months after the last dose of investigational drug (www.swissmedicinfo.ch).

Exclusion Criteria:

- Any pathological evidence of small-cell carcinoma component

- Presence of any distant metastasis

- History of hematologic or primary solid tumor malignancy, unless in remission for at
least 3 years after registration, with the exception of adequately treated cervical
carcinoma in situ, localized non-melanoma skin cancer or low risk localized prostate
cancer (T1-T2a, Gleason <7, PSA <10ng/ml)

- Residual urinary bladder volume after micturition > 150ml (measured by ultrasound of
bladder or inserted catheter)

- Prior treatment for bladder cancer including BCG instillations. Single dose
intravesical chemotherapy instillation after TURB is allowed

- Bladder surgery or traumatic catheterization or TURB within 14 days prior to the
expected start of BCG trial treatment

- Uncontrollable urinary tract infection, macroscopic haematuria, suspicion of bladder
perforation, urethral strictures (if interfering with trial procedures)

- Any conditions preventing the patient from keeping BCG instillation in the bladder
for at least 1 hour anticholinergics are allowed to achieve this criterion

- Any previous treatment with a PD-1 or PD-L1 inhibitor, including atezolizumab

- Concomitant or prior use of immunosuppressive medication within 28 days before
registration, with the exceptions of intranasal and inhaled corticosteroids, or
systemic corticosteroids which must not exceed 10 mg/day of prednisone (or a dose
equivalent corticosteroid) and the premedication for chemotherapy

- Concurrent treatment with other experimental drugs or other anticancer therapy,
treatment in a clinical trial within 28 days prior to registration

- Major surgical procedure within 28 days prior to registration

- Preexisting peripheral neuropathy (> grade 1)

- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criterion:

- Patients with vitiligo or alopecia

- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement

- Any chronic skin condition that does not require systemic therapy

- Patients without active disease in the last 5 years may be included but only
after consultation with the Coordinating Investigator

- Patients with celiac disease controlled by diet alone

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment

- Known history of tuberculosis, known history of primary immunodeficiency, known
history of allogeneic organ transplant, or receipt of live attenuated vaccine within
4 weeks prior to registration, or anticipation of need for such a vaccine during
atezolizumab treatment or within 5 months after the final dose of atezolizumab

- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
IV), unstable angina pectoris, history of myocardial infarction within the last six
months, serious arrhythmias requiring medication (with exception of atrial
fibrillation or paroxysmal supraventricular tachycardia), significant
QT-prolongation, uncontrolled hypertension

- Any concomitant drugs contraindicated for use with the trial drugs according to the
approved product information

- Known hypersensitivity to trial drugs or to any component of the trial drugs

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications. (ICTRP)

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Critères d'évaluation principaux et secondaires
Pathological complete remission (pCR) (ICTRP)

Event-free survival (EFS);Recurrence-free survival (RFS) after R0 resection;Overall survival (OS);Quality of resection: Complete resection;Quality of resection: Completeness of the lymphadenectomy and surgery;Quality of resection: Postoperative complications;Pathological response (PaR) rate;Pattern of recurrence;Treatment feasibility;Adverse events (ICTRP)

Date d'enregistrement
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Inclusion du premier participant
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Sponsors secondaires
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Contacts supplémentaires
Richard Cathomas, MD;Sabrina Chiquet, trials@sakk.ch, +41 31 389 91 91, Kantonsspital Graub?nden, Chur, (ICTRP)

ID secondaires
SAKK 06/19 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04630730 (ICTRP)